For more than 50 years we have known that glutamate is the main excitatory neurotransmitter in the brain but we have much more to learn about the function and regulation of glutamate. Our laboratory intends to elucidate the role of glutamate in sensory ganglia, which is the area of the nervous system where all primary sensory neurons are located. While the importance of the sensory ganglion in transmitting pain signals is undeniable, the function of glutamate in the ganglion has not been studied. Our recent experiments provide evidence that there is a significant release of glutamate in sensory ganglia, where it activates pain neurons. To firmly establish the role of glutamate in the ganglion, it is critical that we show its effects occur through receptors and that there are glutamate related changes in the ganglia following nerve injury. The experiments we propose involve pharmacologic modulation of glutamate receptors on sensory neurons to determine the behavioral effects. We will also use electrophysiological recording from whole, intact ganglia to determine the effects of glutamate on specific receptors in the ganglion. Using electron microscopy, we will also locate the cells in the sensory ganglion that have glutamate receptors on their surface that enables them see glutamate. From a scientific point of view these findings will provide a solid foundation for the notion that there is chemical communication (cross-excitation) between sensory neurons through non-synaptic (volume) transmission. This will lead to a comprehensive view of the neurochemical events occurring around sensory neurons. These findings will bring a fresh understanding of the sensory ganglion as a dynamic area where key chemical phenomena are involved in various forms of pain, from migraines, to intractable facial pain, from fibromyalgia to chronic low back pain. The sensory ganglion is an ideal area to study volume transmission, which is now being implicated in brain disorders such as epilepsy and schizophrenia.